title: Clinical, functional, and radiographic benefits of longterm adalimumab plus methotrexate: final 10-year data in longstanding rheumatoid arthritis.
abstract: OBJECTIVE
  To examine the longterm effectiveness and safety of adalimumab in patients with longstanding rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX), and to assess the effect of a 1-year delay in initiation of combination therapy.
  
  
  METHODS
  DE019 was a 1-year randomized controlled trial (RCT) in which patients received adalimumab 20 mg weekly, adalimumab 40 mg every other week (eow), or placebo; all received concomitant MTX. Patients completing the RCT could receive open-label adalimumab 40 mg eow + MTX for an additional 9 years. Clinical, functional, and radiographic outcomes were assessed using composite measures of disease activity (e.g., American College of Rheumatology responses, 28-joint Disease Activity Score with C-reactive protein, Simplified Disease Activity Index), Health Assessment Questionnaire-Disability Index, and the modified total Sharp score (mTSS), respectively.
  
  
  RESULTS
  Of the 619 patients randomized, 457 entered the open-label extension; 202 completed 10 years. At Year 10, patients demonstrated effective disease control and inhibition of radiographic progression. Differences in clinical and functional responses between adalimumab + MTX and placebo + MTX observed during the RCT became less apparent at Year 10. Still, patients who initially received adalimumab + MTX had significantly lower mean ΔmTSS at Year 10 compared with patients who initially received placebo + MTX. No new safety signals arose following up to 10 years of adalimumab + MTX exposure.
  
  
  CONCLUSIONS
  During up to 10 years of treatment with adalimumab + MTX, patients with longstanding RA experienced effective disease control with no change to the expected safety profile. A 1-year delay in receipt of adalimumab + MTX was associated with reduced effectiveness, suggesting that a window of opportunity to prevent irreversible damage exists even in a population with established RA.
authors.affiliation: University of Toronto, Toronto, Ontario, Canada. keystone@mtsinai.on.ca
authors.forename: Edward C
authors.initials: EC
authors.lastname: Keystone
authors.forename: Désirée
authors.initials: D
authors.lastname: van der Heijde
authors.forename: Arthur
authors.initials: A
authors.lastname: Kavanaugh
authors.forename: Hartmut
authors.initials: H
authors.lastname: Kupper
authors.forename: Shufang
authors.initials: S
authors.lastname: Liu
authors.forename: Benoît
authors.initials: B
authors.lastname: Guérette
authors.forename: Neelufar
authors.initials: N
authors.lastname: Mozaffarian
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D011859:Radiography; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D000068879:Adalimumab; D008727:Methotrexate
keywords: ADALIMUMAB; METHOTREXATE; RANDOMIZED CONTROLLED TRIAL; RHEUMATOID ARTHRITIS